The design of metal complexes and catalysts that are capable of selective bond activation of small molecules has been a longstanding target of the synthetic community. The current paradigm primarily focuses on a single active metal site with ligands that impart steric and electronic tunability to achieve substrate binding and activation, with limited attention paid to the secondary interactions of appended groups. Taking inspiration from biological systems, our group is working to develop strategies to exploit acidic and basic groups (hydrogen bond donors, Lewis acids/bases) to promote cooperative interactions. This presentation will emphasize how Lewis acids can be used to augment metal-based reactivity, as well as to show how incorporation of these units within a ligand scaffold can provide access to unique activation processes.